We are continuing to evaluate polyamines as biochemical markers of cancer. We have further substantiation that the level of putrescine in both plasma and urine accurately reflects the number of cells progressing through cell cycle, whereas spermidine concentration in plasma and urine is related to the cell loss or cell death of putrescine in plasma and urine with the (3H)thymidine labeling index in multiple myeloma patients prior to chemotherapy. The addition of a fluorometer to the Durrum D-500 amino acid analyzer has allowed increased sensitivity so that plasma levels of polyamines can be accurately measured. We are evaluating serial plasma and urine levels of polyamines before, during and after chemotherapy to study fluid dynamics and to assess the proper body fluid for routine measurements of polyamine levels. Long-term follow-up studies of patients in remission are being conducted in order to assess how far in advance of clinical relapse polyamine levels will increase. If sufficient lead time can be obtained by the routine evaluation of polyamine levels, chemotherapy could be reinstituted at the earliest time of a detectable increase in disease activity. Work is in progress to further elucidate the mechanism of induction of ornithine decarboxylase (ODC) in normal and neoplastic growth. We have implicated cyclic AMP-dependent protein kinase as the purported event related to increased genetic transcription and de novo synthesis of the enzyme. We have found also that steroid hormones which have a direct nuclear effect also induce ornithine decarboxylase in target tissues and that the induction is related to de novo synthesis of the enzyme. Further work is in progress related to the relationship between ODC induction and increased RNA polymerase I activity. It still appears that ODC may act as an initiation factor for RNA polymerase I. Studies are in progress in CHO cells related to the mechanism of induction of ODC. In these studies, drugs that arrest at G1/S boundary are used to assess direct effects on ODC or on protein kinase. Because of the importance of polyamine in growth, both normal and neoplastic, and because extracellular polyamine levels appear to reflect pathology, current studies are focused to provide the most rapid transfer of knowledge from the basic studies to the clinical application.